Table 2.
Association of Isolated Second- or Third-Degree Hypospadias with Periconceptional Maternal Medication Usea, National Birth Defects Prevention Study, October 1997 to December 2007.
| Medication Exposure | Exposed Cases (Total cases=1537) | Exposed Controls (Total controls=4314) | OR (95% CI) | Adjusted ORb (95% CI) |
|---|---|---|---|---|
| Antihistamines, First Generation | ||||
| Chlorpheniramine | 37 | 78 | 1.4 (0.9, 2.0) | 1.4 (0.6, 2.1) |
| Diphenhydramine | 38 | 99 | 1.1 (0.7, 1.6) | 1.0 (0. 7, 1.5) |
| Doxylamine succinate | 27 | 68 | 1.1 (0.7, 1.8) | 1.0 (0.6, 1.6) |
| Promethazine | 46 | 148 | 0.9 (0.6, 1.2) | 0.8 (0. 6, 1.1) |
| Antihistamines, Second Generation | ||||
| Cetirizine HCl | 21 | 46 | 1.3 (0.8, 2.2) | 1.0 (0.6, 1.7) |
| Fexofenadine HCl | 22 | 39 | 1.6 (0.9, 2.7) | 1.1 (0.7, 2.0) |
| Loratadine | 46 | 98 | 1.3 (0.9, 1.9) | 1.1 (0.8, 1.6) |
| Antibiotics | ||||
| Amoxicillin trihydrate | 85 | 233 | 1.0 (0.8, 1.3) | 1.0 (0.8, 1.3) |
| Azithromycin | 19 | 70 | 0.8 (0.5, 1.3) | 0.6 (0.4, 1.1) |
| Cephalexin | 10 | 34 | 0.8 (0.4, 1.7) | 0.9 (0.4, 1.8) |
| Nitrofurantoin | 28 | 68 | 1.2 (0.8, 1.8) | 1.3 (0.8, 2.1) |
| Sulfamethoxazole | 15 | 38 | 1.1 (0.6, 2.0) | 1.1 (0.6, 2.0) |
| Trimethoprim | 15 | 38 | 1.1 (0.6, 2.0) | 1.1 (0.6, 2.0) |
| Alpha/Beta Agonists | ||||
| Phenylpropanolamine | 11 | 14 | 2.2 (1.0, 4.9) | 2.0 (0.9, 4.8) |
| Pseudoephedrine | 148 | 392 | 1.1 (0.9, 1.3) | 0.9 (0.7, 1.1) |
| Alpha-Adrenergic Agonists | ||||
| Phenylephrine | 8 | 14 | 1.6 (0.7, 3.9) | 1.6 (0.6, 4.1) |
| Analgesics | ||||
| Acetaminophen | 956 | 2514 | 1.2 (1.1, 1.4) | 1.0 (0.8, 1.1) |
| Aspirin | 93 | 187 | 1.4 (1.1, 1.8) | 1.3 (0.9, 1.7) |
| Codeine | 14 | 42 | 0.9 (0.5, 1.7) | 0.9 (0.4, 1.6) |
| Ibuprofen | 423 | 945 | 1.4 (1.2, 1.6) | 1.2 (1.0, 1.3) |
| Meperidine HCl | 9 | 21 | 1.2 (0.6, 2.6) | 1.2 (0.5, 2.6) |
| Naproxen sodium | 77 | 179 | 1.2 (0.9, 1.6) | 1.0 (0.7, 1.3) |
| Oxycodone | 12 | 21 | 1.6 (0.8, 3.3) | 1.0 (0.5, 2.3) |
| Antidepressants | ||||
| Bupropion HCl | 12 | 26 | 1.3 (0.7, 2.6) | 1.3 (0.7, 2.7) |
| Fluoxetine HCl | 13 | 42 | 0.9 (0.5, 1.6) | 0.9 (0.5, 1.7) |
| Paroxetine | 9 | 29 | 0.9 (0.4, 1.9) | 1.0 (0.5, 2.2) |
| Sertraline HCl | 22 | 48 | 1.3 (0.8, 2.2) | 1.2 (0.7, 2.1) |
| Venlafaxine | 9 | 11 | 2.3 (1.0, 5.6) | 2.4 (1.0, 6.0) |
| Antidiabetic Agents | ||||
| Insulin | 12 | 19 | 1.8 (0.9, 3.7) | 2.1 (0.9, 4.7) |
| Metformin | 7 | 13 | 1.5 (0.6, 3.8) | 0.8 (0.3, 2.2) |
| Barbiturates | ||||
| Butalbital | 8 | 8 | 2.8 (1.1, 7.5) | 2.1 (0.7, 5.8) |
| Beta2-Adrenergic Agonists | ||||
| Albuterol sulfate | 49 | 122 | 1.1 (0.8, 1.6) | 1.1 (0.8, 1.6) |
| Salmeterol xinafoate | 12 | 20 | 1.7 (0.8, 3.5) | 1.7 (0.8, 3.6) |
| Cardiovascular Agents | ||||
| Atenolol | 5 | 10 | 1.4 (0.5, 4.1) | 1.0 (0.3, 3.3) |
| Labetalol | 9 | 6 | 4.2 (1.5, 11.9) | 2.6 (0.9, 7.7) |
| Methyldopa | 9 | 21 | 1.2 (0.6, 2.6) | 1.1 (0.4, 2.5) |
| CNS Stimulants | ||||
| Caffeine | 27 | 52 | 1.5 (0.9, 2.4) | 1.1 (0.7, 1.8) |
| Fertility Agents | ||||
| Progesterone only* | 46 | 71 | 1.8 (1.3, 2.7) | 1.1 (0.7, 1.7) |
| Clomiphene only | 38 | 43 | 2.5 (1.6, 3.9) | 1.9 (1.2, 3.0) |
| FSH+HCG+LEU+PRO | 17 | 11 | 4.4 (2.1, 9.4) | 2.2 (1.0, 4.8) |
| Clomiphene+PRO | 10 | 10 | 2.8 (1.2, 6.8) | 2.0 (0.8, 5.0) |
| FSH+HCG+PRO | 10 | 7 | 4.0 (1.5, 10.6) | 1.7 (0.6, 4.7) |
| FSH+PRO | 7 | 6 | 3.3 (1.1, 9.8) | 1.7 (0.5, 5.4) |
| GI, Antiemetics | ||||
| Ondansetron HCl | 23 | 45 | 1.4 (0.9, 2.4) | 1.0 (0.6, 1.7) |
| GI, Antiflatulants | ||||
| Simethicone | 12 | 33 | 1.0 (0.5, 2.0) | 0.7 (0.3, 1.4) |
| GI, Antiulcer Agents and Acid Suppressants | ||||
| Lansoprazole | 6 | 6 | 2.8 (0.9, 8.7) | 2.8 (0.8, 9.8) |
| Omeprazole | 5 | 5 | 2.8 (0.8, 9.8) | 2.9 (0.7, 11.3) |
| Ranitidine HCl | 11 | 27 | 1.2 (0.6, 2.3) | 0.9 (0.4, 1.9) |
| GI, Digestants | ||||
| Betaine | 5 | 20 | 0.7 (0.3, 1.9) | 0.7 (0.2, 1.8) |
| GI, Prokinetic Agents | ||||
| Metoclopramide | 10 | 21 | 1.3 (0.6, 2.9) | 1.0 (0.5, 2.3) |
| Herbals | ||||
| Alfalfa | 7 | 22 | 0.9 (0.4, 2.1) | 0.7 (0.3, 1.6) |
| Allium sativum, herb | 9 | 25 | 1.0 (0.5, 2.2) | 0.9 (0.4, 2.1) |
| Angelica polymorpha | 8 | 22 | 1.0 (0.5, 2.3) | 0.8 (0.3, 1.8) |
| Barley grass | 10 | 10 | 2.8 (1.2, 6.8) | 2.1 (0.8, 5.4) |
| Bee pollen | 11 | 29 | 1.1 (0.5, 2.1) | 1.1 (0.5, 2.2) |
| Bioflavonoid | 19 | 47 | 1.1 (0.7, 2.0) | 0.8 (0.5, 1.5) |
| Compound | ||||
| Cranberry Concentrate | 6 | 9 | 1.9 (0.7, 5.3) | 1.6 (0.6, 4.6) |
| Echinacea | 11 | 22 | 1.4 (0.7, 2.9) | 1.2 (0.6, 2.7) |
| Ephedra | 8 | 28 | 0.8 (0.4, 1.8) | 1.0 (0. 5, 2.4) |
| Ginger | 17 | 43 | 1.1 (0.6, 2.0) | 1.0 (0.6, 1.9) |
| Ginkgo biloba extract | 8 | 13 | 1.7 (0.7, 4.2) | 1.6 (0.6, 4.4) |
| Ginseng | 10 | 20 | 1.4 (0.7, 3.0) | 1.4 (0.6, 3.2) |
| Herbal tea | 17 | 35 | 1.4 (0.8, 2.5) | 1.8 (1.0, 3.5) |
| Hesperidin Complex | 5 | 6 | 2.4 (0.7, 7.7) | 2.1 (0.6, 7.1) |
| Hydrastis canadensis | 6 | 12 | 1.4 (0.5, 3.8) | 1.6 (0.6, 4.5) |
| Hypericum perforatum | 5 | 6 | 2.4 (0.7, 7.7) | 1.7 (0.5, 5.9) |
| Peppermint | 5 | 13 | 1.1 (0.4, 3.0) | 0.8 (0.3, 2.3) |
| Raspberry leaf | 18 | 33 | 1.5 (0.9, 2.7) | 0.9 (0.5, 1.8) |
| Rutin | 9 | 30 | 0.8 (0.4, 1.8) | 0.7 (0.3, 1.4) |
| Sarsaparilla root | 5 | 8 | 1.8 (0.6, 5.4) | 2.3 (0.7, 7.6) |
| Siberian ginseng | 5 | 13 | 1.1 (0.4, 3.0) | 1.2 (0.4, 3.5) |
| Spirulina | 11 | 26 | 1.2 (0.6, 2.4) | 0.9 (0.4, 1.8) |
| Thea sinesis | 12 | 32 | 1.1 (0.5, 2.1) | 0.9 (0.4, 1.8) |
| Vitis vinifera | 8 | 10 | 2.3 (0.9, 5.7) | 1.9 (0.7, 5.3) |
| Hormonal Contraceptive Medications | ||||
| Estrogen+Progestinc,d | 70 | 212 | 1.0 (0.6, 1.5) | 1.0 (0.7, 1.5) |
| Progestin onlyc,e | 29 | 95 | 1.1 (0.8, 1.5) | 1.9 (1.1, 3.2) |
| Respiratory Agents | ||||
| Dextromethorphan | 51 | 113 | 1.3 (0.9, 1.8) | 1.1 (0.7, 1.5) |
| Guaifenesin | 41 | 120 | 1.0 (0.7, 1.4) | 0.8 (0.6, 1.2) |
| Steroids, Glucocorticoids | ||||
| Budesonide | 6 | 8 | 2.1 (0.7, 6.1) | 1.2 (0.4, 3.7) |
| Fluticasone | 21 | 39 | 1.5 (0.9, 2.6) | 1.1 (0.6, 2.0) |
| Prednisone | 5 | 15 | 0.9 (0.3, 2.6) | 0.6 (0.2, 1.7) |
| Triamcinolone | 5 | 9 | 1.6 (0.5, 4.7) | 1.5 (0.5, 4.9) |
| Thyroid and Antithyroid Agents | ||||
| Levothyroxine sodium | 45 | 71 | 1.8 (1.2, 2.7) | 1.3 (0.9, 2.0) |
| Potassium iodide | 67 | 176 | 1.1 (0.8, 1.4) | 0.8 (0.6, 1.1) |
| Miscellaneous Therapeutic Agents | ||||
| Lactobacillus acidophilus | 5 | 14 | 1.0 (0.4, 2.8) | 0.7 (0.2, 2.0) |
| Glucosamine | 6 | 3 | --- | --- |
| Potassium clavulanate | 8 | 18 | 1.3 (0.5, 2.9) | 1.2 (0.5, 2.8) |
| Royal jelly | 10 | 31 | 0.9 (0.4, 1.9) | 0.8 (0.4, 1.7) |
Abbreviations: OR, odds ratio; CI, confidence interval; BMI, body mass index.
Medication exposure is reported for the period from 1 month before to 4 months after conception.
Odds ratios are adjusted for maternal age, race/ethnicity, education, pre-pregnancy BMI, previous live births, sub-fertility, study site, and year of due date. Fertility agents other than progesterone alone were not adjusted for sub-fertility.
Progesterone use was reported either for subfertility or for pregnancy complications.
Progestin and estrogen compound exposures are in response to questions during the maternal interview about oral contraceptives only and include only exposures through month 3 postconception.
Progestin and estrogen compounds include combinations of the following estrogen compounds: ethinyl estradiol, estradiol cypionate, and NOS-estrogen; and the following progestin compounds: desogestrel, drosperinone, etonogestrel, levonorgestrel, medroxyprogesterone, norelgestromin, norethnidrone, norgestimate, and progestin NOS
Progestin only medications include levonorgestrel, medroxyprogesterone, norethindrone, and progestin NOS
--- Odds ratios were not estimated for medication components with fewer than 5 exposed controls.